{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:22:03Z","timestamp":1792034523689,"version":"4.4.0"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,21]],"date-time":"2023-01-21T00:00:00Z","timestamp":1674259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AI407294"],"award-info":[{"award-number":["AI407294"]}]},{"name":"NIH","award":["AI129302"],"award-info":[{"award-number":["AI129302"]}]},{"name":"NIH","award":["W81XWH-15-1-0616"],"award-info":[{"award-number":["W81XWH-15-1-0616"]}]},{"name":"NIH","award":["DK 116503-01A1"],"award-info":[{"award-number":["DK 116503-01A1"]}]},{"name":"Office of the Assistant Secretary of Defense for Health Affairs through the Defense Medical Research and Development Program","award":["AI407294"],"award-info":[{"award-number":["AI407294"]}]},{"name":"Office of the Assistant Secretary of Defense for Health Affairs through the Defense Medical Research and Development Program","award":["AI129302"],"award-info":[{"award-number":["AI129302"]}]},{"name":"Office of the Assistant Secretary of Defense for Health Affairs through the Defense Medical Research and Development Program","award":["W81XWH-15-1-0616"],"award-info":[{"award-number":["W81XWH-15-1-0616"]}]},{"name":"Office of the Assistant Secretary of Defense for Health Affairs through the Defense Medical Research and Development Program","award":["DK 116503-01A1"],"award-info":[{"award-number":["DK 116503-01A1"]}]},{"name":"NIDDK","award":["AI407294"],"award-info":[{"award-number":["AI407294"]}]},{"name":"NIDDK","award":["AI129302"],"award-info":[{"award-number":["AI129302"]}]},{"name":"NIDDK","award":["W81XWH-15-1-0616"],"award-info":[{"award-number":["W81XWH-15-1-0616"]}]},{"name":"NIDDK","award":["DK 116503-01A1"],"award-info":[{"award-number":["DK 116503-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetes mellitus is a chronic disease characterized by metabolic dysregulation which is frequently associated with diabetic foot ulcers that result from a severely compromised innate immune system. The high levels of blood glucose characteristic of diabetes cause an increase in circulating inflammatory mediators, which accelerate cellular senescence and dampen antimicrobial activity within dermal tissue. In diabetic wounds, bacteria and fungi proliferate in a protective biofilm forming a structure that a compromised host defense system cannot easily penetrate, often resulting in chronic infections that require antimicrobial intervention to promote the healing process. The designed host defense peptide (dHDP) RP557 is a synthesized peptide whose sequence has been derived from naturally occurring antimicrobial peptides (AMPs) that provide the first line of defense against invading pathogens. AMPs possess an amphipathic \u03b1-helix or \u03b2-sheet structure and a net positive charge that enables them to incorporate into pathogen membranes and perturb the barrier function of Gram-positive and Gram-negative bacteria along with fungi. The capacity of skin to resist infections is largely dependent upon the activity of endogenous AMPs that provided the basis for the design and testing of RP557 for the resolution of wound infections. In the current study, the topical application of RP557 stopped bacterial growth in the biofilm of methicillin-resistant Staphylococcus aureus (MRSA) USA300 infected wounds on the flanks of clinically relevant diabetic TALLYHO mice. Topical application of RP557 reduced bacterial load and accelerated wound closure, while wound size in control diabetic mice continued to expand. These studies demonstrate that RP557 reduces or eliminates an infection in its biofilm and restores wound-healing capacity.<\/jats:p>","DOI":"10.3390\/ijms24032143","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T02:27:45Z","timestamp":1674440865000},"page":"2143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A Designed Host Defense Peptide for the Topical Treatment of MRSA-Infected Diabetic Wounds"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-1147","authenticated-orcid":false,"given":"Alex","family":"Vargas","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Davis, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1691-4571","authenticated-orcid":false,"given":"Gustavo","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Davis, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Rivara","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Davis, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Woodburn","sequence":"additional","affiliation":[{"name":"Riptide Bioscience, Inc., Vallejo, CA 94592, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis Edward","family":"Clemens","sequence":"additional","affiliation":[{"name":"Riptide Bioscience, Inc., Vallejo, CA 94592, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1186-6611","authenticated-orcid":false,"given":"Scott I.","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Davis, CA 92037, USA"},{"name":"Department of Dermatology, University of California, Davis, CA 95618, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"573032","DOI":"10.3389\/fendo.2020.573032","article-title":"Cellular Senescence as the Pathogenic Hub of Diabetes-Related Wound Chronicity","volume":"11","year":"2020","journal-title":"Front. 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